瘦素与生殖

瘦素是由脂肪细胞分泌的多肽类激素。它不仅是脂肪组织向大脑传递能量储存信号的信使 ,也是一个循环激素 ,参与体内包括炎症、血管形成、造血、免疫生殖等一系列生理过程。瘦素水平过高或过低都可导致一系列病理变化。本文就瘦素在生殖方面的影响作一综述。1　瘦素生理1.1　概述　瘦素是肥胖基因 ob编码的蛋白质产物 ,由 16 6 /16 7氨基酸组成 ,参与细胞的成熟与生长 ,因此近来被称为 类细胞因子。原先认为瘦素仅在白色脂肪组织合成分泌 ,但随后发现下丘脑、垂体、胃上皮基底部、骨骼肌、合体滋养细胞、乳腺上皮等区域也有瘦素合成分泌。瘦…     

应激与女性生殖内分泌疾病关系的研究进展

躯体和心理应激均能抑制或损害女性生殖内分泌功能。该文就近几年应激导致女性生殖内分泌疾病的机制及对月经周期异常、原发性痛经、经前期综合征，女性生育能力及围绝经期综合征等生殖内分泌疾病影响的研究作以综述。     

运动与下丘脑-垂体-睾丸轴

睾酮作为雄激素的代表,与运动的关系非常密切。关于运动对下丘脑-垂体-睾丸轴的影响,长期以来存在争议。生理状态下,睾酮的相对稳定主要取决于下丘脑和垂体的调控。那么运动后血清睾酮水平的变化主要是下丘脑及垂体调节,还是存在于外周机制,目前尚不明确,有待进一步深入研究。本文就睾酮的生理特性、作用、运动对睾酮代谢的影响及运动影响睾酮代谢的因素做一综述,以供读者参考。     

11β-羟基类固醇脱氢酶1在束缚应激大鼠下丘脑及海马的表达

目的观察应激大鼠下丘脑海马11β-羟基类固醇脱氢酶1(11β-HSD1)的表达变化,探讨11β-HSD1在HPA轴调节中的作用。方法将20只大鼠随机分为对照组、束缚应激组,用Western印迹杂交法观察二组大鼠下丘脑海马内11β-HSD1水平变化。结果束缚应激大鼠海马内11β-HSD1表达水平明显高于对照组(P<0.05),而下丘脑内11β-HSD1表达与对照组比较无统计学差异,但有增加趋势。结论束缚应激能够促进海马内11β-HSD1的表达,其表达增加可能与海马对HPA轴的负反馈调节有关。     

创伤后应激障碍的神经生物学研究进展

创伤后应激障碍(PTSD)是当机体遭受生命威胁或者强烈精神创伤后发生的精神疾病。近年来关于PTSD的机制研究主要包括HPA轴功能失调、神经递质水平异常、谷氨酸系统失衡以及其它相关蛋白表达异常。尽管目前关于PTSD的研究已经取得了较大成就,但其准确的神经生物学机制仍然有待于进一步的研究。     

应激与抑郁症发病的相关性及新药研究进展

重度抑郁症是全球范围内最大的公共卫生难题之一,其具有反复性和周期性,可严重影响患者正常的工作能力和社会活动。应激是指外界刺激影响机体内环境稳态而引起的机体非特异性反应,长期的慢性应激通过激活并损伤下丘脑一垂体．肾上腺（HPA）轴及抑制海马神经元冉生诱发抑郁症。本文就应激、HPA轴在抑郁发病机制中的重要作用以及与该机制相关的抗抑郁药的研究进展进行综述。     

龟鹿二仙胶对创伤后应激障碍大鼠行为学和HPA轴功能的影响

目的观察创伤后应激障碍(PTSD)大鼠下丘脑-垂体-肾上腺(HPA)轴功能和行为学的变化及龟鹿二仙胶对其的影响。方法采用单一延长应激(SPS)的方法建立大鼠PTSD模型,采用旷场实验、高架十字迷宫实验,检测大鼠自主活动及焦虑水平;应用地塞米松抑制实验,检测大鼠HPA轴快速负反馈功能;采用ELISA法检测血浆皮质酮(CORT)水平和促肾上腺皮质激素(ACTH)含量。结果PTSD模型大鼠d 8开始出现HPA轴快速负反馈功能增强,并持续到d 22。模型组大鼠d 8焦虑水平升高,持续到d29。此外,d 29还出现自主活动下降和血浆CORT水平升高。龟鹿二仙胶连续给药14 d后能明显抑制HPA轴负反馈功能的增强;连续给药21 d后能明显提高大鼠的自主活动能力,降低其焦虑水平和血浆CORT水平。结论龟鹿二仙胶能够改善PTSD大鼠的行为学异常,其作用机制可能与调节HPA轴的功能紊乱有关。     

糖皮质激素受体及其调节药物在应激中的作用及机制

海马糖皮质激素受体(GR)参与下丘脑-垂体-肾上腺(HPA)轴功能的负反馈调节,是调控机体应激反应和海马可塑性不可或缺的因素.海马GR可以通过抑制HPA轴关键调节因子促肾上腺皮质激素释放激素(CRH)的转录与合成,实现对HPA轴的负反馈调节,从而促进应激后机体内稳态恢复.但GR长期过度激活将损害海马突触可塑性,影响学习...     

应激启动下丘脑-垂体-肾上腺轴信号转导机制的实验研究

目的以束缚应激大鼠作为应激研究模型,探讨应激后下丘脑内信号转导分子的变化。方法用Western印迹杂交法研究了应激大鼠下丘脑内c-fos的蛋白表达和p38MAPK的磷酸化情况。结果Western印迹杂交结果显示束缚应激后鼠下丘脑内磷酸化的p38MAPK明显增加,与对照组相比具有非常显著性差异(P<0.01),应激解除后1、3h磷酸化的p38MAPK仍然保持较高的水平(P<0.05),但是应激解除后3h较应激刚结束时下丘脑内磷酸化p38MAPK的水平明显回落(P<0.05);应激后下丘脑内c-fos蛋白表达同样明显增加,与对照组相比具有显著性差异(P<0.01)。应激解除后0、1、3h,c-fos蛋白的表达仍然保持较高的水平(P<0.05)。结论应激发生后,其下丘脑内p38MAPK磷酸化的时相、c-fos蛋白表达时相以及血浆内皮质酮浓度时相具有类似之处,p38MAPK磷酸化、c-fos蛋白很可能是HPA轴活动的上游分子信号。     

The endocrine effects of mercury in humans and wildlife

Mercury (Hg) is well studied and research continues as our knowledge of its health risks increases. One expanding area of research not well emphasized to date is the endocrine effects of Hg. This review summarizes the existing literature on the effects of Hg on the endocrine system and identifies gaps in the knowledge. It focuses on the thyroid, adrenal, and reproductive systems, including the accumulation of Hg in the endocrine system, sex differences that are manifested with Hg exposure, reproductive effects in male and female animals including humans, and Hg effects on the thyroid and adrenal systems. We concluded that there are five main endocrine-related mechanisms of Hg across these systems: (a) accumulation in the endocrine system; (b) specific cytotoxicity in endocrine tissues; (c) changes in hormone concentrations; (d) interactions with sex hormones; and (e) up-regulation or down-regulation of enzymes within the steroidogenesis pathway. Recommendations for key areas of research to better understand how the endocrine effects of Hg affect human and wildlife health were developed, and include increasing the amount of basic biological information available about Hg and wildlife species, exploring the role of Hg in the presence of other stressors and chemicals, understanding sublethal and indirect effects of Hg on adverse outcomes, developing better methods to extrapolate effects across species, and understanding the effects of Hg on multiple organ systems following exposure of an animal. Greater inclusion of endocrine endpoints in epidemiological and field studies on humans and wildlife will also advance the research in this area.     

腹腔镜下采用卵巢良性肿瘤剥除对生殖内分泌功能的影响研究

目的：探讨腹腔镜下卵巢良性肿瘤剥除对生殖内分泌功能的影响。方法选取2011年9月～2013年3月来我院就诊的卵巢良性肿瘤患者127例,根据治疗方法分为观察组（79例）及对照组（48例）。对照组采用常规经腹手术,观察组采用腹腔镜进行手术。观察两组患者治疗前后LH、E2、FSH各指标及手术时间、术中出血量、术后下床活动时间及术后住院时间等指标。结果观察组患者治疗前后比较,LH、E2、FSH各指标差异均显著（t=35.136,9.354,12.312,P＜0.05）。对照组患者治疗前后比较,LH、E2、FSH各指标差异均显著（t=28.651,16.357,4.137,P＜0.05）。观察组治疗后LH、E2、FSH各指标与对照组比较,差异有统计学意义（t=29.316,13.168,9.662,P＜0.05）。观察组手术时间、术中出血量、术后下床活动时间及术后住院时间均优于对照组（t分别为7.356,21.245,6.346,9.116,P＜0.05）。观察组的AMH指数,基础窦卵泡数（AFC）及bFSH等指标皆显著高于对照组,差异显著（t分别为6.337,7.365,5.134,P＜0.05）。结论卵巢良性肿瘤剥除具有较好的安全性及可靠性,可以较好的保留患者的生殖内分泌功能。     

Chronic Administration of Monosodium Glutamate under Chronic Variable Stress Impaired Hypothalamic-Pituitary-Adrenal Axis Function in Rats

The hypothalamic-pituitary-adrenal (HPA) axis is the primary endocrine system to respond to stress. The HPA axis may be affected by increased level of corticotrophin-releasing factors under chronic stress and by chronic administration of monosodium glutamate (MSG). The purpose of this study was to investigate whether chronic MSG administration aggravates chronic variable stress (CVS)-induced behavioral and hormonal changes. Twenty-four adult male Sprague-Dawley rats, weighing 200~220 g, were divided into 4 groups as follows: water administration (CON), MSG (3 g/kg) administration (MSG), CVS, and CVS with MSG (3 g/kg) administration (CVS+MSG). In addition, for the purpose of comparing the effect on plasma corticosterone levels between chronic stress and daily care or acute stress, 2 groups were added at the end of the experiment; the 2 new groups were as follows: naïve mice (n=7) and mice exposed to restraint stress for 2 h just before decapitation (A-Str, n=7). In an open field test performed after the experiment, the CVS+MSG group significant decrease in activity. The increase in relative adrenal weights in the CVS and CVS+MSG group was significantly greater than those in the CON and/or MSG groups. In spite of the increase in the relative adrenal weight, there was a significant decrease in the plasma corticosterone levels in the CVS+MSG group as compared to all other groups, except the naïve group. These results suggest that impaired HPA axis function as well as the decrease in the behavioral activity in adult rats can be induced by chronic MSG administration under CVS rather than CVS alone.     

Stress reactivity: biological and subjective responses to the cold pressor and Trier Social stressors

The cold pressor test (CPT) and Trier Social Stress Test (TSST) have been shown to reliably increase HPA activity; however, little research has compared responses to these stressors. In this study, biological (plasma cortisol and ACTH levels) and subjective (e.g., stress and mood) responses were compared in 31 subjects administered both the CPT and TSST. Subjects were diagnosed with alcohol dependence and post-traumatic stress disorder (PTSD) (n = 11), alcohol dependence without PTSD (n = 10), PTSD without alcohol use disorder (n = 4), and neither PTSD nor alcohol use disorder (n = 6). All subjects completed both the CPT and TSST. In all groups, the TSST elicited higher levels of ACTH and cortisol than the CPT, and the response time course differed between tasks. The TSST also produced lower mood ratings than the CPT. A comparison of all diagnosed groups with normal controls revealed group differences in ACTH responding for the CPT but not the TSST. The results suggest that the TSST results in a greater HPA response than the CPT; however, the CPT may have utility in diagnostically heterogeneous patients.     

Cannabinoids Prevent the Development of Behavioral and Endocrine Alterations in a Rat Model of Intense Stress

Cannabinoids have recently emerged as a possible treatment of stress- and anxiety-related disorders such as post-traumatic stress disorder (PTSD). Here, we examined whether cannabinoid receptor activation could prevent the effects of traumatic stress on the development of behavioral and neuroendocrine measures in a rat model of PTSD, the single-prolonged stress (SPS) model. Rats were injected with the CB1/CB2 receptor agonist WIN55,212-2 (WIN) systemically or into the basolateral amygdala (BLA) at different time points following SPS exposure and were tested 1 week later for inhibitory avoidance (IA) conditioning and extinction, acoustic startle response (ASR), hypothalamic-pituitary-adrenal (HPA) axis function, and anxiety levels. Exposure to SPS enhanced conditioned avoidance and impaired extinction while enhancing ASR, negative feedback on the HPA axis, and anxiety. WIN (0.5 mg/kg) administered intraperitoneally 2 or 24 h (but not 48 h) after SPS prevented the trauma-induced alterations in IA conditioning and extinction, ASR potentiation, and HPA axis inhibition. WIN microinjected into the BLA (5 μg/side) prevented SPS-induced alterations in IA and ASR. These effects were blocked by intra-BLA co-administration of the CB1 receptor antagonist AM251 (0.3 ng/side), suggesting the involvement of CB1 receptors. These findings suggest that (i) there may be an optimal time window for intervention treatment with cannabinoids after exposure to a highly stressful event, (ii) some of the preventive effects induced by WIN are mediated by an activation of CB1 receptors in the BLA, and (iii) cannabinoids could serve as a pharmacological treatment of stress- and trauma-related disorders.     

Differences in FKBP51 Regulation Following Chronic Social Defeat Stress Correlate with Individual Stress Sensitivity: Influence of Paroxetine Treatment

Various clinical studies have identified FK506-binding protein 51 (FKBP51) as a target gene involved in the development of psychiatric disorders such as depression. Furthermore, FKBP51 has been shown to affect glucocorticoid receptor signaling by sensitivity modulation and it is implicated in stress reactivity as well as in molecular mechanisms of stress vulnerability and resilience. We investigated the physiological, behavioral, and neuroendocrine parameters in an established chronic stress model both directly after stress and after a recovery period of 3 weeks and also studied the efficacy of paroxetine in this model. We then examined FKBP51 mRNA levels in the dorsal and ventral part of the hippocampus and correlated the expression to behavioral and endocrine parameters. We show robust chronic stress effects in physiological, behavioral, and neuroendocrine parameters, which were only slightly affected by paroxetine treatment. On the contrary, paroxetine led to a disruption of the neuroendocrine system. FKBP51 expression was significantly increased directly after the stress period and correlated with behavioral and neuroendocrine parameters. Taken together, we were able to further elucidate the role of FKBP51 in the mechanisms of stress resilience and vulnerability, especially with respect to behavioral and neuroendocrine parameters. These findings strongly support the concept of FKBP51 as a marker for glucocorticoid receptor sensitivity and its involvement in the development of psychiatric disorders.     

Mycotoxin zearalenone induced gonadal impairment and altered gene expression in the hypothalamic–pituitary–gonadal axis of adult female zebrafish (Danio rerio)

In the present study, we aimed to assess the adverse effects of zearalenone (ZEA) at environmentally relevant concentrations (0.5, 1, 5 and 10 μg l^?1) on hypothalamic–pituitary–gonadal axis associated reproductive function using zebrafish model. ZEA was exposed to female zebrafish for 21 days to assess growth indices such as condition factor, hepatosomatic index, gonadosomatic index and caspase 3 activity. Further, expression of estrogen receptor (ER) α and CYP19a1b genes in the brain, ERα and vitellogenin (Vtg) genes in the liver and follicle‐stimulating hormone receptor, luteinizing hormone receptor, ERα, steroidogenic acute regulatory protein, 3β‐hydroxysteroid dehydrogenase (HSD), 17‐βHSD and CYP19a1 genes in the ovary were also investigated. Our results showed that there were no significant changes in the condition factor and hepatosomatic index, whereas a significant (P < .05) reduction in the gonadosomatic index, increase in caspase 3 activities and Vtg expression was observed at higher concentration. However, no significant changes were observed at lower treatment levels. Further, we also observed significant (P < .05) upregulation in ERα, Vtg, luteinizing hormone receptor, steroidogenic acute regulatory protein, 3β‐HSD, 17β‐HSD, CYP19a1 and CYP19a1b genes in treatment groups with higher levels of ZEA. Moreover, in histopathological examination, we observed oocyte atresia and oocyte membrane detachment in ovaries at the highest concentration. In conclusion, the present study revealed the negative impact of ZEA on zebrafish reproductive system by involvement of the hypothalamic–pituitary–gonadal axis‐associated reproductive function.     

达英-35联合生活方式调整对肥胖型多囊卵巢综合征生殖内分泌和脂代谢的影响

目的探讨达英-35联合生活方式调整对肥胖型多囊卵巢综合征的临床治疗疗效。方法选择2009年5月～2011年5月到笔者所在医院就诊的79例肥胖型多囊卵巢综合征患者,分为实验组45例,给予达英-35联合生活方式调整治疗;对照组34例,单给予达英-35治疗。比较两组治疗前后的生殖内分泌和脂代谢等指标的变化及促排卵情况。结果经治疗后两组的生殖内分泌、脂代谢指标均有下降,实验组下降更为明显,差异有统计学意义(P<0.05)。治疗组的排卵率及受孕率均高于对照组,差异有统计学意义(P<0.05)。结论达英-35联合生活方式调整治疗肥胖型多囊卵巢综合征可明显改善患者的生殖内分泌和脂代谢情况,提高患者的排卵率和受孕率。     

Alterations in endocrine responses in male Sprague-Dawley rats following oral administration of methyl tert-butyl ether.

Methyl tert-butyl ether (MTBE) is an oxygenated fuel additive used to decrease carbon monoxide emissions during combustion. MTBE is a nongenotoxic chemical that induces Leydig cell tumors (LCT) in male rats. The mechanism of MTBE-induced LCT is not known; however, LCT induced by other nongenotoxic chemicals have been associated with the disruption of the hypothalamus-pituitary-testicular (HPT) axis. The objective of this study was to determine whether MTBE functions as an endocrine-active compound by affecting levels of specific hormones involved in the maintenance of the HPT axis. Nine-week-old male Sprague-Dawley rats were administered MTBE by gavage at 0, 250, 500, 1000, or 1500 mg MTBE/kg/day for 15 or 28 consecutive days and sacrificed 1 h following the last dose. Relative testis weights were increased only in high-dose animals treated for 28 days, and no testicular lesions were observed at any dose level. Adrenal gland, liver, and kidney weights were also increased. Histologic changes included protein droplet nephropathy of the kidney and centrilobular hypertrophy of the liver. Interstitial fluid and serum testosterone levels as well as serum prolactin levels were decreased only in animals treated with 1500 mg MTBE/kg/day for 15 days. At 28 days, serum triiodothyronine (T3) was significantly decreased at 1000 and 1500 mg MTBE/kg/day compared to control animals, and a decrease in serum luteinizing hormone and dihydrotestosterone was observed at 1500 mg MTBE/kg/day. These results indicate that MTBE causes mild perturbations in T3 and prolactin; however, the changes in testosterone and LH levels did not fit the pattern caused by known Leydig cell tumorigens.